Am. J. Trop. Med. Hyg., 88(2), 2013, pp. 292–300
Copyright © 2013 by The American Society of Tropical Medicine and Hygiene
Maternal Anemia in Pregnancy: Assessing the Effect of Routine
Preventive Measures in a Malaria-Endemic Area
Smaı ¨la Oue ´draogo,* Ghislain K. Koura, Florence Bodeau-Livinec, Manfred M. K. Accrombessi,
Achille Massougbodji, and Michel Cot
Unite ´ Mixte de Recherche 216, Me `re et Enfant Face aux Infections Tropicales, Paris, France; Faculte ´ des Sciences de la Sante ´, Cotonou, Benin;
Faculte ´ de Pharmacie, Universite ´ Paris Descartes, Paris, France; Ecole des Hautes Etudes en Sante ´ Publique, Rennes, France
during pregnancy. Anemia (hemoglobin < 110 g/L) was common: 68.3% at first antenatal visit (ANV1), 64.7% at second
antenatal visit (ANV2), and 40.6% at delivery. Parasitic infections and nutritional deficiencies were the most preventable
causes. After intermittent preventive treatment (IPTp) and antihelminthic treatments, malaria prevalence decreased from
15.1% (ANV1) to 4.0% (ANV2) and increased again to 9.6% at delivery. Helminth infections dropped from 11.1%
(ANV1) to 7.2% (ANV2) and 2.4% at delivery. Malaria was associated with lower mean hemoglobin on ANV1 and
delivery, and iron deficiency was associated with lower mean hemoglobin on ANV1 and ANV2. IPTp and antihelminthic
treatments were efficacious to clear parasitic infections and improve hematologic status, whereas the effectiveness of daily
iron and folic acid supplements to correct iron and folate deficiencies and decrease anemia was less marked, possibly
because of lack of compliance.
We investigated the effectiveness of routine preventive measures for anemia in Beninese pregnant women
Gestational anemia is common in developing countries,
where it affects more than 57% of pregnancies1,2and
adversely impacts the course of gestation and its outcomes.3
In Benin, a previous study showed that over 60% of women
experience anemia during gestation.4The causes of maternal
anemia are complex, including infections (malaria and hel-
minth infestations), nutrient deficiencies (iron, folic acid, and
vitamin B12), and genetic factors (hemoglobinopathies).5–7
In a preceding article, we had found that potentially prevent-
able causes, such as micronutrient deficiencies and parasitic
diseases, were the main factors associated with anemia in
Beninese pregnant women in early pregnancy.8
Because of hemodilution and increasing needs of iron and
other nutrients for both the mother and the fetus, hemoglobin
(Hb) levels decrease progressively in pregnancy, whereas in
the third trimester, hemoconcentration results in higher Hb
levels.9,10To prevent the consequences of gestational anemia
on mother’s health and pregnancy outcomes, several mea-
sures have been recommended by the World Health Organi-
zation (WHO), including the administration of a daily iron
and folic acid supplement in pregnant women11and the pre-
ventive treatment of malaria and intestinal helminths with
sulfadoxine-pyrimethamine intermittent preventive treatment
(SP-IPTp)12and mebendazole (or albendazole), all adminis-
tered at antenatal visits (ANVs).13
Although widely implemented, the effectiveness of such
preventive measures in sub-Saharan Africa still needs to be
documented, because the information is incomplete and
sometimes conflicting.14,15After our first study in Benin,
which was conducted before the administration of any treat-
ment or supplement, we followed a cohort of pregnant women
included in a clinical trial of IPTp, aiming to assess the effec-
tiveness of routine antimalarials, antihelminthic treatments,
and hematinics on the main etiologies that we had found and
their global effectiveness on maternal anemia at different
time points of gestation.
MATERIALS AND METHODS
Study design. We followed a cohort of 1,005 pregnant
women participating in Malaria in Pregnancy Preventive
Alternative Drugs (MiPPAD; http://clinicaltrials.gov/ct2/show/
NCT00811421), a randomized trial of IPTp with either SP or
Study site and population. The study site and population
have been described elsewhere.8Briefly, the study was
conducted in the district of Allada, a semirural area located
in southern Benin. Malaria is perennial, and Plasmodium
falciparum is the most common species. There are two high
transmission peaks: from April to July and from October to
November. The MiPPAD study population was composed
of human immunodeficiency virus (HIV) -negative pregnant
women of less than or equal to 28 weeks gestational age who
attended one of three study maternity clinics of the area for
the first time between January of 2010 and May of 2011. The
eligibility criteria included no intake of IPTp, iron, folic acid,
vitamin B12, or antihelminthic treatment, which are part of the
ANV package in Benin, since the beginning of the pregnancy.
Two doses of IPTp (1,500/75 mg SP per dose or 15 mg/kg MQ
per dose) were administered on ANVs. The second dose of
IPTp was given at least 1 month apart from the administration
of the first dose. On the day of inclusion, each woman received
a long-lasting insecticide-treated net that was replaced in case
of damage or loss during the follow-up. Women were also
systematically given 600 mg albendazole to be taken at home
(100 mg two times per day for 3 days) according to the guide-
lines of the Beninese Ministry of Health. In addition, sup-
plements of oral ferrous sulfate (200 mg per day) and folic acid
(5 mg per day) were given to the women for home treatment
(Figure 1). Pregnant women found to have a Hb concentration
below 110 g/L were treated according to the severity of anemia
(i.e., 200 mg oral ferrous sulfate two times per day for mild
or moderate anemia when Hb was between 70 and 110 g/L)
and referred to the tertiary hospital of the district in case of
severe anemia (Hb < 70 g/L). All the medications prescribed
*Address correspondence to Smaı ¨la Oue ´draogo, Unite ´ Mixte de
Recherche 216, Me `re et Enfant Face aux Infections Tropicales/
Faculte ´ des Sciences de la Sante ´, 4, avenue de l’Observatoire, 75270
Paris, France. E-mail: email@example.com
to the women during their participation in the study were free
Study procedures. Sociodemographic data collection. At
enrolment (ANV1), all pregnant women who attended any
of the maternity clinics for ANV were approached to partici-
pate in the study. They were screened for inclusion and exclu-
sion criteria, and sociodemographic data, such as age, parity,
area of residence, marital status, level of education, occu-
pation, and socioeconomic characteristics (sanitation in the
house, personal means of transportation, possession of fridge
or television, and connection to electricity), were recorded.
ANV1 was also the occasion to administer antiparasitic treat-
ments and nutritional supplements to the women.
Clinical data collection. At ANV1, the woman was exam-
ined, and parity, gestational age, middle upper arm circumfer-
ence, weight, and height were recorded. Medical history,
including history of previous pregnancies, history of any
known disease (such as high blood pressure, diabetes, or
asthma), and information on previous children (birth weight,
gestational age at delivery, and notion of anemia during
previous pregnancy), was also recorded.
At the time of ANV2, at delivery, and during the unsched-
uled visits, gestational age, middle upper arm circumference,
weight, and height were measured again. The second intake
of IPTp was also given on ANV2. Weights were measured
to the nearest 0.1 kg using an electronic scale (SECA
France, Semur-en Auxois, France), and heights were mea-
sured to the nearest 0.1 cm with a SECA bodymeter device
Blood and stool samples collection. At ANV1, ANV2, and
delivery, 8 mL venous blood were collected from each partic-
ipant; 4 mL were dispensed into a dipotassium (ethylene-
dinitrilo)tetraacetic acid (EDTA) tube, and 4 mL were
dispersed into a dry iron-free tube. A container was also given
to the woman to collect stools in search of intestinal hel-
minths. These containers were collected the next day by the
study nurses within the first 6 hours after emission.
At delivery, a placental blood smear was performed to
look for placental malaria (Figure 1).
Laboratory tests. The study sample examination techniques
have been described elsewhere.8Hb rate was measured with
a Hemo_Control photometer (EKF Diagnostics, Magdeburg,
Germany) on 10 mL blood.
Hb genotypes were determined by alkaline electrophoresis
on cellulose acetate (Helena Laboratories, Mount Waverley,
Victoria, Australia) on 50 mL blood.
Figure 1.Study procedures.
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OUE´DRAOGO AND OTHERS